ANALYSISANALYSIS ARTICLE 23(96), March - April, 2019

ISSN 2321–7359 EISSN Medical Science 2321–7367

The effect of stem extract on blood pressure and weight of type 2 diabetic patients

Fahimeh Shojaei-Shad1, Maryam Jahantigh-Haghighi2, Ali Mansouri2, Mahdieh Jahantigh-Haghighi3

Background and aim: Diabetes is a serious chronic disease that can damage the heart, blood vessels, eyes, kidneys and nerves, leading to death and early disability. Blood glucose control can prevent these complications. Also, a decrease in systolic blood pressure reduces the risk of each complication of diabetes and the risk of death from diabetes. Rhubarb is prescribed in traditional medicine for various patients, including patients with diabetes, high blood lipids and high blood pressure. However, its effect has not been scientifically reported. This study aimed to determine the efficacy of Rhubarb stem extract on hypertension and weight of type II diabetic patients. Methods: In this experimental study, 80 diabetic patients with type 2 diabetes mellitus in the city of Zabol, aged 30- 60 years old, fasting blood glucose greater than 140 mg /dl and hypertension above 140/90 mmHg, after matching they were randomly divided into two groups of 40 patients treated with Rivas stem capsules and placebo. Patients in both groups were evaluated for blood pressure and weight before and after the study. Results: The mean systolic blood pressure and diastolic blood pressure in the rhubarb group before and after the intervention were 144.87 ± 8.73 and 95.75 ± 7.72, respectively, after intervention, to 133.95 ± 10.98 and 83.73 ± 25.28% decrease. Paired t-test and Wilcoxon showed a significant decrease in systolic and diastolic blood pressure and diastolic blood pressure with rhubarb intervention (p <0.05), but no significant changes were observed in intervention and weight loss control groups (p <0.05). Conclusion: The use of 400 mg Rhubarb stem capsules three times a day in type 2 diabetic patients can significantly decrease systolic blood pressure and diastolic blood pressure, but there is a significant difference in weight loss between the two groups before and then the intervention did not work.

INTRODUCTION kidneys and nerves, leading to death and early disability (1). Diabetes Diabetes is a serious chronic illness, (1) with more than 220 million complications include skin lesions, hypertension and weight gain (9), people worldwide in 2010, the prevalence of diabetes in the world is and vascular complications of diabetes, including nerve fibrosis, 4.6%, which is between 3.8% and 2.10% of the closure Variable Nephropathy and retinopathy and macrovascular diseases, which are the geographic area (2). Type 2 diabetes is associated with tissue resistance leading cause of mortality in diabetic patients. Blood glucose, as well as to insulin and a relative lack of insulin secretion, although insulin is high blood pressure and high blood lipids, contribute to the risk of produced by beta cells in these patients, but this amount is not sufficient cardiovascular disease 9. High blood pressure is one of the risk factors to overcome insufficient resistance, resulting in increased blood glucose that, if not controlled, accelerate the progression of complications of (3). diabetes, especially cardiovascular problems. The UKPDS study showed The World Health Organization estimates that Type-2 diabetes will that any reduction in mmHg10 in systolic blood pressure causes a 12 rise from 171 million to 366 million in 2030. (4) Studies also show that percent reduction in the risk of each complication of diabetes and a 15 in 2025 more than 75% of the total population of diabetics in the country percent reduction in the risk of death from diabetes [10]. (5) 4 to 5 million people with diabetes live in (6). The World Health The number of people with diabetes is rapidly increasing due to Organization (WHO) has reported it as an underlying epidemic (7), population growth, population aging, urbanization and industrialization, considering the increasing incidence of diabetes in the world. and an increase in the prevalence of obesity and physical inactivity (11). Diabetes mellitus is characterized by symptoms such as Type 2 diabetes is associated with an increase in mortality and a decline hyperglycemia, urination, fatigue, weight loss, delayed healing of the in quality of life. Therefore, it puts a lot of economic burden on health wounds, blurred vision, increased glucose in the urine, and some other systems and society (12). symptoms (8). The importance of this disease is due to the prevalence of To control diabetes, changes in lifestyle need to be made. Evidence its complications. Diabetes can damage the heart, blood vessels, eyes, suggests that if you have adequate blood glucose control, you can prevent or delay the long-term complications of diabetes (13). The 1Msc in Nursing, Zabol University of Medical Sciences, Zabol, Iran; 2Msc in

Nursing, Instructor, Faculty of Nursing and Midwifery, Zabol University of Medical primary treatment of type 2 diabetes is oral antidiabetic drugs (14). 159 3 Sciences, Zabol, Iran; Bsc in Nursing, Faculty of Nursing and Midwifery, Zahedan These drugs have disadvantages such as drug resistance development,

University of Medical Sciences, Zahedan, Iran; Page Corresponding Author: Maryam Jahantigh-Haghighi, Faculty of Nursing and side effects and even toxicity to response deficiencies. Moreover, none Midwifery, Zabol University of Medical Sciences, Zabol, Iran. of these glucose lowering drugs effectively control blood lipid levels.

© 2019 Discovery Publication. All Rights Reserved. www.discoveryjournals.org OPEN ACCESS

ANALYSIS ARTICLE

Table 1 Comparison of FBS, HBA1C, systolic and diastolic blood pressure mean in Rhubarb group and placebo group before and after intervention Rhubarb group Placebo group Group p-value p-value Before intervention After intervention Before intervention After intervention FBS 288/80±94/49 226/42±88/89 0/0001 252/55±82/98 252/72±85/33 0/94 HBA1C 9/62±1/58 7/83±1/50 0/0001 9/52±1/67 9/49±1/68 0/72 Systolic blood 144/78±8/73 133/50±10/98 0/0001 145/20±9/04 143/75±11/91 0/31 pressure diastolic blood 95/75±7/72 85/25±8/83 0/0001 95/37±8/72 93/37±7/95 0/19 pressure

Table 2 Comparison of the mean weight before and after taking Rhubarb and placebo Variable Before intervention After intervention T Df p-value

Mean of weight in Rhubarb group 74/97±10/98 75/83±12/89 1/43 21 0/15

Mean of weight in placebo 75/85±12/19 75/26±10/83 0/713 39 0/48

Therefore, with the increasing prevalence of diabetes and the adverse the patient by the therapist without any knowledge of it, and a special effects of synthetic drugs, there is a clear need for the development of code was inserted in the patient's file. Patients in the intervention group natural herbal resources for anti-diabetic drugs (9). received a can of 90 capsules of 400 mg (daily 3 am, noon, night) of the is a that is known as the family stem extract of the rhubarb plant and the placebo group was similarly (15), known as Rush, Rhubarb, or Rivend. Rhubarb root is used to treat delivered to a can of 90 mg placebo capsules. Patients in both groups diabetes, (15) and (16) hypertension, ulcers, obesity, diarrhea, and were evaluated for systolic and diastolic blood pressure and weight at sputum (17). Rhubarb has a laxative effect and is used to treat the end of the study after a month. constipation. Its root extract is also used to treat diabetes, stomach, liver, smallpox and rubella. Antioxidant properties and the presence of FINDINGS in rhubarb, including quercetine, have been effective on The findings of this study showed that the mean age of subjects in the blood glucose and metabolic disorders in diabetes. (18). One of the most intervention group was 50.22 6.72 and in the control group (placebo) important properties of rhubarb is that it causes the pancreas to secrete 50.57 ± 6.60. The mean weight before the study in the intervention insulin and hence reduces blood glucose (19, 20). Rhubarb reduces lipid group was 74.97 ± 10.98 and 75.85 ± 12.19 in the control group. 27.5% and blood pressure (21) and, in combination with cinnamon, has an anti- of the participants in both control and intervention groups were male (n fatty and diabetes effect (22). Due to the increased prevalence of = 11) and 72.5% female (n = 29). Most of the research units were diabetes and cardiovascular and death problems, the result of this study illiterate in both control and control groups (65%) and intervention was to determine the efficacy of rhubarb stem extract on blood pressure (72.5%). There was no significant difference between the individuals in and weight in type 2 diabetic patients. the intervention and control groups in terms of demographic factors (p <0.05). Based on independent t-test and Mann-Whitney test between the METHOD two intervention and control groups in terms of systolic and diastolic This experimental study was performed on 80 patients with type 2 blood pressure and weight There was no significant difference (p <0.05). diabetes mellitus in Zabol city. Subjects were randomly divided into two The mean of systolic blood pressure in the intervention group groups of 40 patients receiving rhubarb and placebo extract. The criteria (rhubarb) before and after the intervention was 144.87 ± 8.73 and after for entering the study include ages 35-60 years, type 2 diabetes for at intervention was 133.50 ± 10.98. Based on Wilcoxon's statistical test, least 6 months, fasting blood glucose greater than 140 mg/dl for at least this reduction in cytological blood pressure after rhubarb intervention 0> two trials, systolic blood pressure above 140 mmHg and pressure p was meaningful. Diastolic blood pressure greater than 90 mm Hg, speaking ability, ability The mean of systolic blood pressure in the control group (placebo) to move and do activity, and not having late-onset diabetes was 45.15 ± 9.04 before placebo, which was 143.71 ± 11.91 after complications such as cardiovascular disease, foot ulcer, eye problems placebo. There was no significant difference between systolic blood According to physician, lack of Alzheimer's disease or mental illness pressure before and after placebo based on Wilcoxon test (p = 0.31). and Psychiatric, non-pregnancy or lactation was the absence of any The mean diastolic blood pressure in the intervention group autoimmune disorder (6.23). Exit criteria included severe physical (rhubarb) before and after the intervention was 95.75 ± 7.72 and 88.25 ± illness, drug discontinuation in diabetes control, oral glucose lowering 8.73 after intervention, which according to Wilcoxon statistical test, this drugs to insulin therapy, reluctance to use capsules, unwillingness to decrease in diastolic blood pressure after rhubarb intervention 0> p was participate in research, use of cigarettes, alcohol and drugs. After meaningful. explaining the purpose of the study for patients and obtaining written The mean diastolic blood pressure in the control group (placebo) informed consent, a general information questionnaire including before the placebo was 95.37 ± 8.72, which was 93.37 ± 7.95 after

demographic information (24) and information about the disease were placebo. Based on the Wilcoxon test, there was no significant difference completed by interviewing each patient. Then, for both groups, blood between diastolic blood pressure before and after placebo (p = 0.19). pressure measurements Systolic and diastolic and weight. All patients The mean of weight before intervention in the rhubarb and placebo

160 were urged to continue their blood glucose-lowering drugs without any group was 74.97 ± 10.98 and 75.85 ± 12.19, which was 73.35 ± 12.82 changes. The 90-gauge package of drug and placebo capsules was and 83.75 after intervention in the intervention group, respectively. / 10 Page similar in appearance and was given by a special code and delivered to ± 26/75. There was no significant difference between the mean of

© 2019 Discovery Publication. All Rights Reserved. www.discoveryjournals.org OPEN ACCESS

ANALYSIS ARTICLE

Figure 1 Mean of variables in intervention group 350

300

250

200

150

100

50

0 FBS HBA1C SBP DBP

Before After

weight before and after intervention in both groups of rhubarb and liver enzymes SGOT, SGPT and creatinine, indicating the health and placebo (p> 0.05); (Table 2), (Figure 1). safety of rhubarb (27). The study by Baha'addini, titled "The Effect of Rhubarb Flower on the Blood and Alcoholic Extract of Rhubarb Flower DISCUSSION on Blood Pressure in Male Rats," also showed a decrease in mean The results of this study indicate that the mean systolic and diastolic arterial pressure, systolic and diastolic pressure, and a significant blood pressure in the control group (placebo) before the placebo was decrease in heart rate in the intervention group compared with the 45.15 ± 9.04 and 95.37 ± 8.72, respectively, which was 91 / 143.75 ± 11 control. We are glad to use the Rhubarb flower in the study of and 93.37 ± 9.99, respectively. Based on the Wilcoxon test, there was no Bharwand, but in the present study, Rhubarb stem has been used. In his significant difference in systolic and diastolic blood pressure after study, Baharvand states that after acetylcholine injection in both control placebo (p = 0.31). The mean of systolic blood pressure in the rhubarb and rhythm tests, heart rate decreased, but in the experimental group it group before and after the intervention was 144.87 ± 8.73 and after the decreased more than the control group, as a result of the effect of intervention was 133.50 ± 10.98. Based on Wilcoxon statistical test, this decreased blood pressure on the possible rat. It can be rhubarb through decrease in cytological blood pressure after rhubarb intervention was> p the chronotropic effect of the heart (28). Hypertension is also rapidly was meaningful. The mean diastolic blood pressure in the rhubarb group associated with the accumulation of plaque atherosclerosis in the arterial before and after the intervention was 95.75 ± 7.72 and 88.25 ± 8.73 after wall (26). Therefore, the effects of rhubarb hypertension can be intervention, which according to the Wilcoxon statistical test, this attributed to the antioxidant, triglyceride and cholesterol (18, 27) effects. decrease in diastolic blood pressure after rhubarb intervention with p <0.05 Was meaningful. The mean of weight before intervention in the CONCLUSION rhubarb and placebo group was 74.97 ± 10.98 and 75.85 ± 12.19, which Since blood glucose control can prevent serious complications of was 73.35 ± 12.82 and 83.75 after intervention in the intervention group, diabetes, as well as a decrease in blood pressure, it reduces the risk of respectively. / 10 ± 26/75. There was no significant difference between any complication of diabetes and the risk of death from diabetes. the mean of weight before and after intervention in both groups of Therefore, the current study, considering the effects of Rhubarb stem on rhubarb and placebo (p> 0.05). the reduction of weight and blood pressure in diabetic patients, it is Considering the above findings, consumption of oral capsules of suggested that plant herbal remedies, especially rhubarb, should be rhubarb stem can significantly decrease blood pressure in type 2 diabetic considered in the treatment schedule of these patients, and extensive patients. The study of Baharond Ahmadi (2016), used as herbal remedy research into the effects of this herb in diabetic type 2 patients should be for cardiovascular disorders, also shows the effects of rheumatoid considered. arthritis (26), which is consistent with our study. Baharvand also states that antioxidant activity is one of the most important biological effects REFERENCES of medicinal , and this effect is mainly related to the presence of 1. World Health Orgenization. Global report on diabetes. 2016.

secondary metabolites, especially phenolic compounds, and medicinal 2. Mcculloch K, Nathan M. Overview of medical care in adults with plants such as rhubarb with antioxidant effects in the treatment of high diabetes mellitus. [Homepage on the Internet]. C2013 [updated: Jan blood pressure can Be effective. The study of Hamza and Fallah also 30, 2013; cited 2014 Nov 9]. Available at: http://www.uptodate.com. 161 3. Shakibi A, Habibi Sh. Basic clinical pharmacology Katzung, Bertram emphasize the antioxidant effects of this plant (18,27). Also, in the study Page G 11 th ed. Tehran, Rafie Publishers: 2009 of Fallah Hosseini, this had no effect on the level of

© 2019 Discovery Publication. All Rights Reserved. www.discoveryjournals.org OPEN ACCESS

ANALYSIS ARTICLE

4. Abbasian M, Delvarian zade M. Diabetes complications in diabetic for the treatment of hypertension. Journal of renal injury prevention. patients referred to the clinic City Shahrod. Journal of Knowledge & 2016;5(3):123. Health 2003;2(4):15-9 26. Fallah Hossini H, FakhrZade H, Larijani B, Sheikh Samani A. A review 5. Talaei B, Mozaffari-Khosravi H, Jalali B, Mahammadi SM, Najarzadeh of medicinal plants used in diabetics. Diabetes Special Issue. A, Fallahzadeh H. The effect of ginger on blood glucose, lipid and 2005;5:1-8. lipoproteins in patients with type 2 diabetes: a double-blind 27. Nikeghbal H. Study the Effect of aqueous and alcoholic extract of randomized clinical controlled trial. J Shahid Sadoughi Univ Med Sci rhubarb flower on blood pressure in male rats. Master's thesis in 2012; 20(3): 383-95. animal physiology: Shiraz University; 2013. 6. Mirzaei M, moghimi M. pharmacology Katzvng- terror First Edition, 28. Smeltzer, S. C. Bare, B. G. Hinkel, J. L. and Cheever, K. h. Brunner Tehran, samat Publishers 2002: 386. and Suddarth's of medical surgical nursing. 13, editor. Tehran: 7. Shaw J.E, Sicree P.Z, Zimmet P.Z. Global estimates of the Philadelphia: Lippincott Williams and Wilkins; 2014. prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4-14 Article Keywords 8. Bathaie SZ, Mokarizade N, Shirali S. An Overview of the Mechanisms Rhubarb, Blood Pressure, Weight, Type 2 diabetes of Plant Ingredients in the Treatment of Diabetes Mellitus. Journal of Medicinal Plants. 2012;11(4):1-24. Thanks and appreciation 9. Ebadi AR, Rahimi Lenge A, Taghadosi M, Khorshidi A. Effect of garlic This article is the result of a research project at Zabol University of on blood sugar in patients with type 2 diabetes. Journal of Faz. Medical Sciences, funded by this university. The professors of the Nursing 2006;11(1):20-5. and Midwifery Faculty of Zabol University of Medical Sciences, the 10. Afkhami Ardekani M, Kamali Ardekani AR. The effect of garlic on honorable authorities of the diabetes center of Zabol city and all the blood pressure in patients with type II diabetes. For two months, the patients who helped us in this project, are appreciated and appreciated. scientific - research Shahed University.2008;16(77):1-6 The code for this article is zbmu.1.REC.1396.118. 11. Rakhshanderou S, Gafari M, Heydarnia A. Rajab A. The effectiveness of educational intervention on metabolic control in diabetic patients Article History referred to Iranian Diabetes Association. Iranian Journal of Diabetes Received: 28 November 2018 and Lipid Disorders. 2009:57-64. Accepted: 16 January 2019 12. Eliades M, Pittas AG, Vitamin D and type 2 diabetes. Clinical Reviews Published: March-April 2019 in Bone and Mineral Metabolism. 2009; 7(2): 185-98. 13. Mahmoodi A. Effect of self care education on decreasing HbA1C Citation among diabetic patients. Medical Sciences Journal of Islamic Azad Fahimeh Shojaei-Shad, Maryam Jahantigh-Haghighi, Ali Mansouri, University 2006;16(3):171-6. Mahdieh Jahantigh-Haghighi. The effect of Rhubarb stem extract on blood 14. Afkhami-ardekani M, Jafaryzadeh HR. Outcome of reinitiation of pressure and weight of type 2 diabetic patients. Medical Science, 2019, combination anti diabetic oral therapy in insulin treated patients with 23(96), 159-162 Type 2 Diabetes Mellitus;journal Tabibe Shargh. Yazd, Iran;2005;7(1):9-14 Publication License 15. Tosun F, Kizilay CA. Anthraquinones and flavonoids from Rheum ribes. Ankara Ecz Fak Derg 2003;32(1):31-5. This work is licensed under a Creative Commons Attribution 16. Sindhu R, Kuamr P, Kumar J, Kumar A, Arora S. Investigations into 4.0 International License. the antiulcer activity of rheum Ribes Linn leaves extracts. Int J Pharm

Pharm Sci. 2010;2(4):90-3. General Note 17. Adham A, Naqishbandi A. HPLC analysis and antidiabetic effect of Rheum ribes root in type 2 diabetic patients. Zanco J Med Sci. Article is recommended to print as color digital version in recycled 2015;19(2). paper. Save trees, save nature 18. Hamzeh S, Farokhi F, Heidari R, Manaffar R. The effect of hydroalcoholic extract of rhubarb root on blood glucose and histopathological changes of pancreas in alloxan-induced diabetic rats. Qom Univ Med Sci J 2010;8(5):20-6. 19. Sargolzaei MS, Mansouri A, Shahdadi H, Masinaei NN, Poodineh MM. The effect of dill tablet on the level of fasting blood sugar in patients with type ii diabetes. 2017. 20. Sobhani Z, Reza Nami S, Ahmad Emami S, Sahebkar A, Javadi B. Medicinal plants targeting cardiovascular diseases in view of Avicenna. Current pharmaceutical design. 2017;23(17):2428-43 21. Yetiş C, Arslanoğlu ŞF, editors. Rheum ribes L. as Medicinal Plant. Congress Book; 2017. 22. Broadhurst CL, Polansky MM. Insuline like biological activity of culinary and medicinal plant aqueous extract in vitro. J Agrc food chem 2000. 48(3): 849- 852. 23. Li LS, Liu ZH. Clinical and experimental studies of Rheum on preventing progression of chronic renal failure. ZhongXi Yi Jie He Za Zhi .991;11(7):392-6, 387. 24. Pourverdi SH, Mohammadi Shahboulaghi F, Kashaninia Z, Rezasoltani P. Effects of self-management program on glycemic

control in patients with type 2 diabetes and glycosylated 162 hemoglobin.2013:25(78); 19-28 25. Baharvand-Ahmadi B, Bahmani M, Tajeddini P, Rafieian-Kopaei M, Page Naghdi N. An ethnobotanical study of medicinal plants administered

© 2019 Discovery Publication. All Rights Reserved. www.discoveryjournals.org OPEN ACCESS